Arsenic is a well-known human carcinogen, which potentially affects ~160 million people worldwide via exposure to unsafe levels in drinking water. lungs are one of the main target organs for arsenic-related carcinogenesis. these tumors exhibit particular features, such as squamous cell-type specificity and high incidence among never smokers. arsenic-induced malignant transformation is mainly related to the biotransformation process intended for the metabolic clearing of the carcinogen, which results in specific genetic and epigenetic alterations that ultimately affect key pathways in lung carcinogenesis. based on this, lung tumors induced by arsenic exposure could be considered an additional subtype of lung cancer, especially in the case of never-smokers, where arsenic is a known etiological agent. in this article, we review the current knowledge on the various mechanisms of arsenic carcinogenicity and the specific roles of this metalloid in signaling pathways leading to lung cancer.
This study is a systematic review based on internal databases including sid, iranmeddex, magiran and authentic english databases including scopus, pubmed, as well as articles and reviewed the letters that have met the inclusion criteria, were examined.
Lung cancer is the leading cause of cancer related deaths in north america, affecting over 200,000 men and women each year. arsenic poisoning through contaminated drinking water leading to arsenic-induced lung cancer is a major public health concern; consequently, the mechanisms underlying the carcinogenic effects of arsenic in lung cancer has become an important avenue of research. undoubtedly, the biotransformation of asv into asiii and its methylated conjugates plays a crucial role in arsenic carcinogenicity at both genetic and epigenetic levels. genetic changes are acquired mainly through the induction of ros during the biotransformation process, while the competition for methyl groups between asv detoxification enzymes and dmts contribute to epigenetic abnormalities. arsenic species directly modulate several oncogenic pathways most notably the egfr, pi3k/akt and the nrf2/keap1 pathways and these specific pathways possess actionable targets for therapy in lung cancer. a greater understanding of the molecular mechanisms governing arsenic-related lung tumorigenesis may therefore yield promising translatable findings. deep characterization of arsenic related tumors and/or cell models at both the genetic and epigenetic levels, and the comparison of arsenic-related and unrelated sqcc tumors may provide such insights. on the other hand, mechanisms associated with anti-tumoral effects of as2o3 in the treatment of apl (not discussed in this review) should also be considered in order to increase the understanding of the molecular effects of arsenic in the human body.
In conclusion, arsenic can induce specific alterations affecting pathways that drive malignant transformation in lung cells. current evidence suggests that arsenic-induced lung tumors represent a unique class of lung cancer, based on histology and underlying molecular characteristics. further characterization of the mechanisms by which arsenic affects its targets will certainly give support to preventing and/or reducing the effects of arsenic toxicity, especially among those populations chronically exposed to arsenic.
Arsenic, arsenite lung, cancer epigenetic reactive, oxygen species epidermal growth factor receptor